There has been a recent striking increase in the incidence of clear-cell adenocarcinoma of the genital tract in young females as a result of prenatal exposure to stilbestrol. A Registry has been established to investigate in depth the epidemiology, clinico-pathologic features, therapy and survival in all cases of these tumors that are occurring throughout the United States and abroad. All cases of clear- cell adenocarcinoma of the genital tract in young women under the age of 30 years will be investigated in detail whether or not there is a history of maternal medication. These studies should establish the natural history of the disease, its optimal therapy, as well as the potential of hormones other than stilbestrol in the pathogenesis of these cancers. A detailed study is also being carried out from a research population of young females whose mothers were treated with known dosages of stilbestrol during pregnancy 12 to 25 years ago, and a control population delivered at the same hospital is also being examined. Vaginal adenosis has been found in approximately one-third of stilbestrol-exposed females and in almost all cases of vaginal adenocarcinoma. The optimal method of the management of vaginal adenosis that has occurred in the stilbestrol-exposed population will be investigated including the possibility of therapy with local progesterone. Female siblings of exposed patients will be examined to investigate any familial tendency to develop vaginal adenosis. Experiments utilizing subhuman primates are underway in an attempt to develop an animal model of stilbestrol-induced abnormalities in the offspring and to study the metabolism of stilbestrol. This supplemental research application is submitted to allow the continuation of these studies that are funded but have greatly expanded in scope and depth since the initial application (CA-13139-01).